Liu Liping, Liu Jilong, Shao Di, Deng Qiuhua, Tang Hailing, Liu Zu, Chen Xuewei, Guo Fengming, Lin Yongping, Mao Mao, Kristiansen Karsten, Ye Mingzhi, He Jianxing
State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, China.
The Translational Medicine Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Cancer Sci. 2017 Dec;108(12):2487-2494. doi: 10.1111/cas.13410. Epub 2017 Oct 20.
People of East Asian ethnicity have a different prevalence of and show unique clinical characteristics and tumor histology of oncogenic mutations. However, only limited studies have explored the landscape of genomic alterations in lung adenocarcinoma derived from Asian patients thus far. In this single-center study, with an aim to elucidate the mutational profile of lung cancer in people of Chinese ethnicity and to use the obtained information to guide decision-making for treatment, we employed a well-validated assay to perform comprehensive genomic characterization of tumor specimens from 306 Chinese lung cancer patients. A total of 845 individual genomic alterations were found in 145 tumor-related genes with a median of 2.8 alterations (range: 1-18) per sample. The most frequently mutated genes were EGFR (46.7%), TP53 (21.2%), ALK (12.1%; 8.8% of mutation and 3.3% of rearrangement) and KRAS (10.1%). Upon comparison with the Cancer Genome Atlas dataset, we found that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS was only found in 10.1% of our Chinese patients. Clinically relevant genomic alterations were identified in 185 (60.5%) patients, including 50% in adenocarcinoma patients and 14% in squamous cell carcinoma patients. Our findings suggest that the Asian ethnicity is significantly different from the Caucasian ethnicity with regard to the presence of somatic driver mutations. Furthermore, we showed that the use of a comprehensive genotyping approach could help identify actionable genomic alterations that have potential impact on therapeutic decisions.
东亚族裔人群致癌突变的患病率不同，且表现出独特的临床特征和肿瘤组织学特征。然而，迄今为止，仅有有限的研究探索了亚洲患者来源的肺腺癌基因组改变情况。在这项单中心研究中，为了阐明中国族裔人群肺癌的突变谱，并利用所获得的信息指导治疗决策，我们采用了一种经过充分验证的检测方法，对306例中国肺癌患者的肿瘤标本进行了全面的基因组特征分析。在145个肿瘤相关基因中总共发现了845个个体基因组改变，每个样本的改变中位数为2.8个（范围：1 - 18个）。最常发生突变的基因是表皮生长因子受体（EGFR，46.7%）、肿瘤蛋白p53（TP53，21.2%）、间变性淋巴瘤激酶（ALK，12.1%；8.8%为突变，3.3%为重排）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS，10.1%）。与癌症基因组图谱数据集相比，我们发现EGFR在我们的队列中的突变频率远高于白种人，而KRAS仅在10.1%的中国患者中被发现。在185例（60.5%）患者中鉴定出了具有临床相关性的基因组改变，其中腺癌患者中占50%，鳞状细胞癌患者中占14%。我们的研究结果表明，在体细胞驱动突变的存在方面，亚洲族裔与白种人有显著差异。此外，我们表明使用全面的基因分型方法有助于识别对治疗决策有潜在影响的可操作基因组改变。
